Delineating the Hemostaseome as an aid to individualize the analysis of the hereditary basis of thrombotic and bleeding disorders.

Next-generation sequencing and genome-wide association studies represent powerful tools to identify genetic variants that confer disease risk within populations. On their own, however, they cannot provide insight into how these variants contribute to individual risk for diseases that exhibit complex inheritance, or alternatively confer health in a given individual. Even in the case of well-characterized variants that confer a significant disease risk, more healthy individuals carry the variant, with no apparent ill effect, than those who manifest disease.

Evolutionary conservation and selection of human disease gene orthologs in the rat and mouse genomes.

Background: Model organisms have contributed substantially to our understanding of the etiology of human disease as well as having assisted with the development of new treatment modalities. The availability of the human, mouse and, most recently, the rat genome sequences now permit the comprehensive investigation of the rodent orthologs of genes associated with human disease. Here, we investigate whether human disease genes differ significantly from their rodent orthologs with respect to their overall levels of conservation and their rates of evolutionary change.

The DNA sequence and comparative analysis of human chromosome 10.

The finished sequence of human chromosome 10 comprises a total of 131,666,441 base pairs. It represents 99.4% of the euchromatic DNA and includes one megabase of heterochromatic sequence within the pericentromeric region of the short and long arm of the chromosome.

Genome sequence of the Brown Norway rat yields insights into mammalian evolution.

The laboratory rat (Rattus norvegicus) is an indispensable tool in experimental medicine and drug development, having made inestimable contributions to human health. We report here the genome sequence of the Brown Norway (BN) rat strain. The sequence represents a high-quality 'draft' covering over 90% of the genome.

Identification of potential cell-surface proteins in Candida albicans and investigation of the role of a putative cell-surface glycosidase in adhesion and virulence.

Cell-surface proteins are attractive targets for the development of novel antifungals as they are more accessible to drugs than are intracellular targets. By using a computational biology approach, we identified 180 potential cell-surface proteins in Candida albicans, including the known cell-surface adhesin Als1 and other cell-surface antigens, such as Pra1 and Csa1. Six proteins (named Csf1-6 for cell-surface factors) were selected for further biological characterization.

Hyperglycemia delays rostral initiation sites during neural tube closure.

Neural tube defects contribute greatly to perinatal loss, physical handicap, mental retardation and other developmental defects, yet the mechanisms through which they occur are poorly understood. One hindrance to the study of these defects at the cellular and molecular levels is the low frequency with which they arise in susceptible animals. The present study utilizes a culture system for the study of rodent exencephaly, an animal model of human anencephaly, in which a high frequency of affected animals are obtained by culture in hyperglycemic rat serum.

Prepupal differentiation in Drosophila: distinct cell types elaborate a shared structure, the pupal cuticle, but accumulate transcripts in unique patterns.

The components of the pupal cuticle are the main differentiation products synthesized by both the larval and adult epidermis during the prepupal period of Drosophila development. The pupal cuticle is formed in vitro by imaginal discs in response to a 6 h pulse of 20-hydroxyecdysone (20-HE). We previously described the isolation and initial characterization of four ecdysone-dependent genes (EDGs) whose expression in imaginal discs occurs only in response to a pulse of 20-HE.

Molecular genetics of Delta, a locus required for ectodermal differentiation in Drosophila.

Delta (Dl) is one of the six known zygotic neurogenic genes, each of which is essential for proper segregation of the embryonic ectoderm into neural and epidermal lineages. Molecular analysis of Dl reveals that it is a transcriptionally complex locus that yields multiple maternal and zygotic transcripts. DNA sequence analysis suggests that the predominant product of the locus is a putative transmembrane protein exhibiting homology to blood coagulation factors and epidermal growth factor of vertebrates.

Delta, a Drosophila neurogenic gene, is transcriptionally complex and encodes a protein related to blood coagulation factors and epidermal growth factor of vertebrates.

Delta (D1) is required for normal segregation of the embryonic ectoderm into neural and epidermal cell lineages in Drosophila melanogaster. Loss-of-function mutations in D1 and other zygotic neurogenic loci lead to expansion of the neuroblast population at the expense of the dermoblast population within the ectoderm. Characterization of the transcriptional organization and maternal/embryonic expression within the chromosomal interval corresponding to D1 reveals that the locus encodes multiple transcripts: a minimum of two maternal transcripts, approximately 4.

Prepupal differentiation of Drosophila imaginal discs: identification of four genes whose transcripts accumulate in response to a pulse of 20-hydroxyecdysone.

We have isolated and initially characterized a novel set of four genes expressed during the prepupal differentiation of imaginal discs of Drosophila melanogaster. These four ecdysone-dependent genes are named EDG-42A, EDG-64CD, EDG-78E and EDG-84A-1 based on their respective chromosomal locations. Their expression is like that expected for genes encoding proteins that participate in the formation of the pupal cuticle.

Cytogenetic definition and morphogenetic analysis of Delta, a gene affecting neurogenesis in Drosophila melanogaster.

We have conducted a genetic analysis of a small interval of the third chromosome known to include Delta (Dl), a locus that affects the segregation of the ectoderm into neural and epidermal lineages during embryogenesis and the morphogenesis of some ectodermally derived structures, in Drosophila melanogaster. This analysis has led to the definition of seven independent complementation groups, one of which is Delta, within the interval extending from 91F6-13 to 92A2. Among the extant mutations in these seven loci, only mutations in Dl lead to the so-called neurogenic phenotype: hypertrophy of the nervous system and reduction of the epidermis.

Gene within a gene: nested Drosophila genes encode unrelated proteins on opposite DNA strands.

A pupal cuticle protein gene has been found within an intron of a Drosophila gene that encodes three purine pathway enzymatic activities. The intronic gene is encoded on the DNA strand opposite the purine pathway gene and is itself interrupted by an intron. Whereas the purine pathway gene is active throughout development, the intronic cuticle protein gene is expressed primarily over a 3 hr period in the abdominal epidermal cells of prepupae that secrete the pupal cuticle.